S. Kerry Kornfeld, M.D., Ph.D.

Professor
Developmental Biology

Developmental, Regenerative and Stem Cell Biology Program
Molecular Genetics and Genomics Program
Molecular Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-747-1480

  • 314-747-2004

  • 314-747-2003

  • 314-362-7058

  • 3607 Cancer Research Building

  • kornfeld@wustl.edu

  • http://kornfeldlab.wustl.edu

  • aging, metals, zinc, development, sperm activation, signal transduction, homeostasis

  • organismal aging; zinc homeostasis and roles of zinc during cell differentiation.

Research Abstract:

Our research addresses two areas—organismal aging and the biology of metals during growth and development. Our studies of metals focus on zinc, which is essential for all life. To investigate zinc biology, we combine genetic analysis of C. elegans with biochemical analysis of purified proteins. Because zinc homeostasis pathways have been extensively conserved, we can translate discoveries made in worms into mammalian systems. We have identified a family of zinc transport proteins (CDF) that mediate high zinc homeostasis by sequestering zinc in lysosomes or excreting zinc out of the animal. These transporters are regulated by a zinc sensing transcription factor in the nuclear receptor family that we recently identified in a genetic screen. Low zinc homeostasis is mediated by a second family of transporters (ZIP) that import zinc into the cytoplasm. We are characterizing the transcriptional control of these transporters by low zinc. We discovered that one ZIP transporter mediates zinc signaling during sperm activation. We hope to understand how animals sense both high and low zinc and maintain homeostasis, and how zinc is used as a second messenger to transmit information during sperm activation.

The progressive, degenerative changes that occur as animals age are of fundamental importance, yet poorly understood. C. elegans is well suited for investigating aging, since it has a short life span of ~18 days. We have characterized phenotypic changes that occur as worms age, and we have identified a class of anticonvulsant drugs and a hypertension medicine that delay age-related degeneration. We hope to define regulatory circuits that control aging and develop therapies that delay aging.

Selected Publications:

Kumar S, Egan BM, Kocsisova Z, Schneider DL, Murphy JT, Diwan A, Kornfeld K. Lifespan Extension in C. elegans Caused by Bacterial Colonization of the Intestine and Subsequent Activation of an Innate Immune Response. Dev Cell. 2019 Apr 8;49(1):100-117.e6. doi: 10.1016/j.devcel.2019.03.010. PubMed PMID: 30965033.

Kocsisova Z, Kornfeld K, Schedl T. Rapid population-wide declines in stem cell number and activity during reproductive aging in C. elegans. Development. 2019 Apr 23;146(8). pii: dev173195. doi: 10.1242/dev.173195. PubMed PMID: 30936182; PubMed Central PMCID: PMC6503983.

Zhao Y, Tan CH, Krauchunas A, Scharf A, Dietrich N, Warnhoff K, Yuan Z, Druzhinina M, Gu SG, Miao L, Singson A, Ellis RE, Kornfeld K. The zinc transporter ZIPT-7.1 regulates sperm activation in nematodes. PLoS Biol. 2018 Jun 7;16(6):e2005069. doi: 10.1371/journal.pbio.2005069. eCollection 2018 Jun. PubMed PMID: 29879108; PubMed Central PMCID: PMC5991658.

Dietrich N, Schneider DL, Kornfeld K. A pathway for low zinc homeostasis that is conserved in animals and acts in parallel to the pathway for high zinc homeostasis. Nucleic Acids Res. 2017 Nov 16;45(20):11658-11672. doi:
10.1093/nar/gkx762. PubMed PMID: 28977437; PubMed Central PMCID: PMC5714235.

Warnhoff K, Roh HC, Kocsisova Z, Tan CH, Morrison A, Croswell D, Schneider DL, Kornfeld K. The Nuclear Receptor HIZR-1 Uses Zinc as a Ligand to Mediate Homeostasis in Response to High Zinc. PLoS Biol. 2017 Jan 17;15(1):e2000094. doi: 10.1371/journal.pbio.2000094. eCollection 2017 Jan. PubMed PMID: 28095401; PubMed Central PMCID: PMC5240932.

Kumar S, Dietrich N, Kornfeld K. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span. PLoS Genet. 2016 Feb 26;12(2):e1005866. doi: 10.1371/journal.pgen.1005866. eCollection 2016 Feb. PubMed PMID: 26918946; PubMed Central PMCID: PMC4769152.

Roh HC, Collier S, Guthrie J, Robertson JD, Kornfeld K. Lysosome-related organelles in intestinal cells are a zinc storage site in C. elegans. Cell Metab. 2012 Jan 4;15(1):88-99. doi: 10.1016/j.cmet.2011.12.003. PubMed PMID: 22225878; PubMed Central PMCID: PMC4026189.

Collins JJ, Evason K, Pickett CL, Schneider DL and Kornfeld K.
http://www.ncbi.nlm.nih.gov/pubmed/18949032" The Anticonvulsant Ethosuximide Disrupts Sensory Function to Extend C. elegans Lifespan. PLoS Genetics 2008 4(10):e1000230. (Abstract)

Hughes S, Evason K, Xiong C and Kornfeld K.
http://www.ncbi.nlm.nih.gov/pubmed/17305431 Genetic and pharmacological factors that influence reproductive aging in nematodes. PLoS Genetics 2007 3(2): 254-265. (Abstract)

Evason K, Huang C, Yamben I, Covey DF and Kornfeld K.
http://www.ncbi.nlm.nih.gov/pubmed/15653505 Anticonvulsant medications extend worm life-span. Science 2005 307: 258-262. (Abstract)

Last Updated: 8/5/2019 10:46:16 AM

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